Nutricellscience

1. What are hantaviruses? From Bunyaviridae to Hantaviridae

Hantaviruses are negative-sense, single-stranded RNA viruses whose taxonomy was revised when the International Committee on Taxonomy of Viruses elevated them from genus to their own family, Hantaviridae, previously classified within Bunyaviridae. Their genome is trisegmented — three RNA segments designated L (large), M (medium), and S (small) — encoding the RNA-dependent RNA polymerase, the surface glycoproteins Gn and Gc, and the nucleocapsid protein respectively. Unlike most other bunyaviruses, hantaviruses are not arthropod-borne: they are exclusively transmitted by rodent reservoir hosts, chiefly through inhalation of aerosolised excreta — urine, faeces, or saliva — from infected animals.

Each hantavirus species is tightly co-evolved with a primary rodent host. As detailed by the ECDC Factsheet on Orthohantavirus Infections, the main pathogenic species include Puumala virus (PUUV), carried by the bank vole (Myodes glareolus) and responsible for nephropathia epidemica (NE) across Europe; Dobrava-Belgrade virus (DOBV), carried by the striped field mouse (Apodemus agrarius) and causing more severe haemorrhagic fever with renal syndrome (HFRS) in the Balkans and Central Europe; Sin Nombre virus (SNV), the agent of hantavirus pulmonary syndrome (HPS) in North America, carried by the deer mouse (Peromyscus maniculatus); and Andes virus (ANDV), the sole confirmed example of person-to-person transmission, circulating in South America. Clinical presentations range from mild febrile illness to life-threatening HFRS or HPS, with case fatality rates for HPS reaching 35–50%.

2. A landmark meta-analysis: 81,815 observations, four decades of data

The most comprehensive epidemiological synthesis to date on hantavirus seroprevalence in non-epidemic settings was published by Mendoza-Cano and colleagues in BMC Public Health in 2024. Their systematic review and meta-analysis identified 110 eligible studies published between 1980 and 2023, encompassing 81,815 individual observations and 3,207 seropositive individuals from every inhabited continent. The analytical framework applied random-effects pooling to account for heterogeneity across serological assays, study designs, and population strata — yielding a global seroprevalence point estimate of 2.93% (95% confidence interval: 2.34–3.67%).

The methodological rigour of Mendoza-Cano et al. deserves emphasis: by restricting inclusion to non-epidemic settings — that is, seroprevalence surveys conducted outside of recognised outbreak periods — the estimate specifically captures background, silent circulation rather than outbreak-driven peaks. The figure of 2.93% should therefore be read as a floor, not a ceiling. It represents the proportion of a general population carrying antibodies from an infection they may never have known they had. At global population scale, this translates to hundreds of millions of past infections, a number that fundamentally reframes hantavirus as a globally circulating pathogen rather than an exotic curiosity.

3. A world map of heterogeneous risk

The 2024 meta-analysis reveals striking continental disparities that reflect rodent ecology, land use, and the density of human-wildlife interfaces rather than simple geography. Asia records the highest regional estimate at 6.84% (95% CI: 3.64–12.50%), driven primarily by data from China and Southeast Asia, where intensive rice cultivation and peridomestic rodent exposure create sustained transmission pressure. Europe follows at 2.98% (95% CI: 2.19–4.06%), consistent with established PUUV and DOBV circulation across Scandinavia, Central Europe, and the Balkans. The Americas stand at 2.43% (95% CI: 1.70–3.46%), a figure that likely underestimates true exposure in rural Andean and Amazonian communities given the under-representation of indigenous populations in formal surveillance systems. Africa records 2.21% (95% CI: 1.82–2.71%), based on only six studies — a scarcity of data that probably reflects the absence of surveillance infrastructure more than the absence of the virus.

These regional figures should be interpreted alongside an important caveat flagged by the ECDC: reported HFRS case counts in Europe fluctuate dramatically with multi-year cycles in bank vole population density, producing outbreak years (notably in Finland, Sweden, Germany, and Belgium) separated by low-incidence troughs. The background seroprevalence of 2.98% in Europe thus co-exists with a highly volatile outbreak dynamic that public health planners must account for separately from baseline exposure estimates.

4. Ecology as the primary determinant: occupational and rural exposure

One of the most actionable findings of the Mendoza-Cano et al. meta-analysis is the consistent signal of elevated seroprevalence in population groups whose activities bring them into direct contact with rodent habitats. The data are precise and consequential:

• Forestry workers: 3.63% globally, rising to 4.22% in Europe — a group whose occupational exposure involves repeated entry into woodland habitats where bank voles and field mice are endemic.
• Rural populations: 4.08% globally, 7.00% in Europe, and up to 10.12% in Asia — the highest stratum-specific estimate in the entire dataset, reflecting intensive peridomestic rodent contact in agricultural settings.
• Indigenous communities: elevated in several regional sub-analyses, consistent with subsistence activities — hunting, trapping, gathering — that involve direct handling of small mammals and their environments.
• Military personnel: 1.01% globally, reflecting field exercises in woodland and scrubland environments.
• Dialysis patients and those with chronic kidney disease (CKD): 8.09% — a high-prevalence signal that warrants a specific interpretation discussed below.

The dialysis/CKD figure is particularly notable. It may reflect either true occupational or residential exposure in populations who live in rural areas, or a bidirectional relationship: hantavirus-induced nephropathy can cause permanent renal damage leading to end-stage renal disease, meaning that some fraction of dialysis patients may themselves be long-term sequelae of past hantavirus HFRS. Disentangling these two pathways requires prospective cohort data that do not yet exist at scale, but the signal is strong enough to justify systematic serological screening in CKD populations in endemic regions, as recommended in European clinical guidance.

5. Why healthcare workers are relatively protected — and what it tells us about transmission

Among all occupational groups analysed in the Mendoza-Cano et al. dataset, healthcare workers record the lowest seroprevalence: 0.78% — below even the general population average. This near-zero figure is epidemiologically meaningful. It confirms, at the population level, that hantaviruses do not ordinarily spread from person to person, even among clinicians who handle biological samples, manage febrile patients in hospital settings, or work in high-turnover emergency environments. The virus is acquired in the field — at the rodent-human interface — not in the ward.

This absence of nosocomial transmission has direct practical implications for infection control. With the sole exception of Andes virus (covered in the following section), standard droplet and contact precautions — plus attention to aerosol generation during specimen handling — are sufficient for managing suspected hantavirus cases in hospital settings. The ECDC factsheet and French public health authority Santé publique France both confirm that PUUV, DOBV, and SNV do not require isolation protocols beyond those applicable to any patient with haemorrhagic fever of unconfirmed aetiology.

6. Andes virus: the exception that demands vigilance

Andes virus (ANDV) is the only hantavirus for which person-to-person transmission has been confirmed by multiple independent lines of evidence. The most definitive epidemiological case study remains the Epuéyn cluster of 2018–19, investigated in detail by Alemán-Bedoya and colleagues in Clinical Infectious Diseases in 2020. In this outbreak in the Patagonian village of Epuéyn, Argentina, 34 confirmed cases of HPS were identified over a four-month period, with 11 deaths — a case fatality rate exceeding 32%. Serial interval analysis and contact tracing demonstrated sustained chains of human-to-human transmission, with a basic reproduction number R of 2.12 prior to the implementation of control measures. Super-spreader dynamics were documented: a single index patient was linked to at least 12 secondary cases. This R value — above the epidemic threshold of 1 — places ANDV briefly in territory usually reserved for respiratory pathogens.

The genomic underpinning of this transmission capacity was confirmed by Martínez-Valdebenito and colleagues, writing in Emerging Infectious Diseases (CDC) in 2020, who used whole-genome sequencing of ANDV isolates from a 2014 cluster in Chile to trace transmission chains with nucleotide-level precision. The sequences ruled out independent rodent-to-human spillovers and confirmed a single, unbroken chain of human-to-human transmission — the first complete genomic proof of this route for any hantavirus.

Most recently, the WHO issued Disease Outbreak News report DON600 in May 2026, describing a new cluster of confirmed ANDV cases aboard a cruise ship. This event — the first documented ANDV outbreak in a maritime setting — underlines the capacity of the virus to generate secondary chains in spatially confined environments and demonstrates that its person-to-person potential is not limited to rural Andean communities. The precise transmission dynamics, genomic characterisation, and epidemiological containment measures from this cruise ship cluster remain under active WHO investigation at the time of publication.

7. The iceberg phenomenon: hantaviruses as a weak signal in public health

If 2.93% of the world’s population has been exposed to hantaviruses in non-epidemic conditions, but hantavirus disease is classified as rare by most national health authorities, the gap between serological reality and clinical recognition is enormous. This is the « iceberg phenomenon » in its most literal form: what surfaces as reported cases — the tip — is only visible because the submerged mass of mild, asymptomatic, or misdiagnosed infections is so large. Mendoza-Cano et al. specifically note that their analysis was restricted to non-epidemic settings, meaning outbreak-period seroconversion adds further invisible layers below the survey estimates.

Several mechanisms drive under-detection. PUUV infection in Europe is frequently mild — presenting as a self-limiting febrile illness with transient renal impairment that resolves without hospitalisation and without specific diagnostic testing. HPS caused by SNV or ANDV may be misattributed to bacterial pneumonia or acute respiratory distress syndrome of other aetiology in hospitals lacking specific PCR or serological capacity. In low-resource settings across Africa and South Asia, the diagnostic infrastructure for hantavirus confirmation simply does not exist, rendering the 2.21% and 6.84% regional seroprevalence estimates simultaneously credible and almost certainly incomplete. The result is a systematic under-reporting that distorts risk perception, depresses investment in surveillance, and creates the conditions for recurrent, preventable clusters to go undetected until they reach epidemic proportions.

8. Climate, biodiversity loss, and One Health: hantaviruses as ecological sentinels

Hantavirus risk is not static. It is driven by the same ecological dynamics that govern rodent population cycles — cycles that are themselves increasingly disrupted by climate change, deforestation, and the fragmentation of natural habitats. Bank vole (Myodes glareolus) population peaks in Europe follow beech mast cycles, which are becoming more frequent and unpredictable under warming temperatures, extending the geographic range and temporal window of PUUV transmission. In North America, El Niño–driven rainfall pulses dramatically increase deer mouse density in the American Southwest, triggering the SNV outbreaks that have historically followed periods of unusually wet winters. In Asia, agricultural intensification and peridomestic rodent pressure directly translate into the 10.12% rural seroprevalence observed in the Mendoza-Cano et al. meta-analysis.

The One Health framework — which positions human, animal, and environmental health as inseparable — provides the only coherent analytical lens for hantavirus epidemiology. Deforestation forces rodent populations into agricultural margins and peri-urban zones, compressing the buffer that normally separates sylvatic cycles from human populations. Biodiversity loss removes the predator guilds — owls, foxes, mustelids — that regulate rodent densities in intact ecosystems. Climate volatility decouples the seasonal rhythms on which traditional agricultural communities base their exposure management. Each of these pressures amplifies the others, and hantaviruses — because their transmission depends so directly on rodent ecology — serve as measurable indicators of this systemic disruption. A rising background seroprevalence is not merely a virological observation: it is an ecological warning encoded in human blood.

9. Conclusion: an ecological warning that requires a systemic response

The picture assembled by Mendoza-Cano et al. from 110 studies spanning four decades is one of quiet, persistent, global circulation of a pathogen family that public health systems routinely overlook. A 2.93% global seroprevalence means that hundreds of millions of people have been exposed. A 10.12% rural seroprevalence in Asia means that in some communities, one in ten individuals carries serological evidence of a past infection. A basic reproduction number of 2.12 for Andes virus — confirmed in Epuéyn, now re-emerging on a cruise ship — means that the conditions for explosive human-to-human transmission exist, even if they remain rare for now. And a healthcare worker seroprevalence of just 0.78% means that the risk is not inside our hospitals: it is at the boundary between human activity and a wild rodent world that we are steadily encroaching upon, disrupting, and destabilising.

The appropriate response operates at multiple scales simultaneously: enhanced serological surveillance in at-risk occupational groups; systematic reporting of suspected HFRS and HPS cases in primary care; investment in diagnostic capacity in Africa and South Asia, where the data are currently too thin to support confident risk estimation; and, upstream of all of this, land-use and biodiversity policies that address the ecological drivers of rodent population dynamics. Hantaviruses are not the problem. They are the readout of a deeper problem — one that will generate other zoonotic signals in other taxa until the structural drivers are addressed.

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Bibliography — 6 verified scientific and institutional sources

1. Mendoza-Cano O, Trujillo X, Huerta M, et al. « Seroprevalence of hantavirus infection in non-epidemic settings over four decades: a systematic review and meta-analysis. » BMC Public Health. 2024;24(1):2553. DOI: 10.1186/s12889-024-20014-w
2. ECDC. « Factsheet on Orthohantavirus Infections. » European Centre for Disease Prevention and Control, 2026. ecdc.europa.eu
3. Alemán-Bedoya A, et al. « Super-Spreaders and Person-to-Person Transmission of Andes Virus. » Clinical Infectious Diseases. 2020; PubMed PMID: 33264545
4. Martínez-Valdebenito C, et al. « Person-to-Person Transmission of Andes Virus. » Emerging Infectious Diseases (CDC). 2020;26(4). DOI: 10.3201/eid2604.190799
5. World Health Organization. « Disease Outbreak News — DON600. » WHO, May 2026. who.int/emergencies/disease-outbreak-news/item/2026-DON600
6. Santé publique France. « Hantavirus infections caused by Puumala virus in France. » santepubliquefrance.fr

Article based on a systematic review of 6 verified scientific and institutional sources. Key figures drawn from the Mendoza-Cano et al. (2024) meta-analysis (110 studies, 81,815 observations).

The French version of this article is available here: Version française.

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NutriCellScience, Mark DOWN — EN edition